Dr Keith Miller BSc, PhD, FHEA
Senior Lecturer in Microbiology
Summary
Keith was appointed as a lecturer at Sheffield Hallam University after completing a BSc and a PhD in Medical Microbiology at the University of Leeds. Also at the University of Leeds, he completed three post-doctoral research fellowships funded by the Department of Health, Novartis and the MRC. During his teaching career at Sheffield Hallam he has taught microbiology and biochemistry and is the course leader for MSc Biomedical Sciences and MSc Biomedical Laboratory Sciences. He is a Fellow of the Higher Education Academy and a member of both the American Society for Microbiology and the British Society for Antimicrobial Chemotherapy
Teaching
Keith teaches Medical Microbiology and is course leader for MSc. Biomedical Sciences and MSc. Biomedical Laboratory Sciences.
Research
Keith's research group is interested in all areas of antimicrobial chemotherapy research. We are investigating new sources of antimicrobial agents including snake and scorpion venom, deep sea corals and novel synthetic drug scaffolds. We are trying to identify and characterise the interactions between drugs and their targets at a molecular level. We are researching genetic, proteomic and biophysical mechanisms of antimicrobial resistance found here in the UK and in the developing world. We are developing novel antimicrobial wound dressing with a broad range of applications.
Natural product antimicrobial drug discovery
The current development gap for novel antimicrobial agents has been well documented. The development of natural products and natural product derivatives has been a rich source of antibiotics in the past and is an area that has been proposed for the development of novel drug development candidates. Peptide antimicrobials from organisms lacking an adaptive immune system and complex organic molecules from natural sources are a relatively underexploited natural product reservoir. These projects seek to establish the mechanism of action of previously identified and purified antimicrobial peptides from snake venoms, scorpion venoms and organic scaffolds from other natural product reservoirs.
Development of antibiotic-resistance
Antibiotic-resistance is an important problem in the management of infectious disease and a major barrier to market-based development of novel antimicrobials. It is important to understand the mechanisms of antimicrobial resistance and the distribution of these mechanisms worldwide. One study conducted here in the BMRC seeks to quantify and characterise carbapenemase resistance determinants in Gram-negative pathogens isolated in three hospitals in the Accra area of Ghana. The rate of carriage, the specific genotypes and the associations with patient information will be determined and assessed for clinical impact.
Publications
Journal articles
Bertelsen, M., Lacey, M., Nichol, T., & Miller, K. (2023). Mechanistic Insight into the Early Stages of Toroidal Pore Formation by the Antimicrobial Peptide Smp24. Pharmaceutics, 15 (10). http://doi.org/10.3390/pharmaceutics15102399
Rawson, K.M., Lacey, M.M., Strong, P.N., & Miller, K. (2022). Improving the therapeutic index of Smp24, a venom-derived antimicrobial peptide: increased activity against gram-negative bacteria. International Journal of Molecular Sciences, 23 (14). http://doi.org/10.3390/ijms23147979
Elrayess, R.A., Mohallal, M.E., Mobarak, Y.M., Ebaid, H.M., Haywood-Small, S., Miller, K., ... Abdel-Rahman, M.A. (2022). Scorpion Venom Antimicrobial Peptides Induce Caspase-1 Dependant Pyroptotic Cell Death. Frontiers in Pharmacology, 12. http://doi.org/10.3389/fphar.2021.788874
Khan, M., Miller, K., Rawson, K., & Zhou, Y. (2021). Synthesis and In Vitro Anti-Helicobacter and Anti-Staphylococcal Activities of Novel Diaryldisulfides and Diarylthiosulfonates. Advances in Biological Chemistry, 11 (5), 251-265. http://doi.org/10.4236/abc.2021.115017
Tawfik, M.M., Bertelsen, M., Abdel-Rahman, M.A., Strong, P.N., & Miller, K. (2021). Scorpion Venom Antimicrobial Peptides Induce Siderophore Biosynthesis and Oxidative Stress Responses in Escherichia coli. mSphere, 6 (3). http://doi.org/10.1128/msphere.00267-21
Elrayess, R.A., Mohallal, M.E., El-Shahat, Y.M., Ebaid, H.M., Miller, K., Strong, P., & Abdel-Rahman, M.A. (2019). Cytotoxic effects of Smp24 and Smp43 scorpion venom antimicrobial peptides on tumour and non-tumour cell lines. International Journal of Peptide Research and Therapeutics, 26 (3), 1409-1415. http://doi.org/10.1007/s10989-019-09932-1
Codjoe, F.S., Brown, C.A., Smith, T., Miller, K., & Donkor, E.S. (2019). Genetic relatedness in carbapenem-resistant isolates from clinical specimens in Ghana using ERIC-PCR technique. PLoS One, 14 (9), e0222168. http://doi.org/10.1371/journal.pone.0222168
Codjoe, F.S., Donkor, E.S., Smith, T., & Miller, K. (2019). Phenotypic and genotypic characterization of carbapenem-resistant gram-negative bacilli pathogens from hospitals in Ghana. Microbial drug resist. http://doi.org/10.1089/mdr.2018.0278
Bao, P., Paterson, D.A., Harrison, P.L., Miller, K., Peyman, S., Jones, J.C., ... Gleeson, H.F. (2019). Lipid coated liquid crystal droplets for the on-chip detection of antimicrobial peptides. Lab on a chip, 19 (6), 1082-1089. http://doi.org/10.1039/C8LC01291A
Heath, G.R., Harrison, P., Strong, P., Evans, S.D., & Miller, K. (2018). Visualization of diffusion limited antimicrobial peptide attack on supported lipid membranes. Soft Matter, 14 (29), 6146-6154. http://doi.org/10.1039/c8sm00707a
Chirila, P., Skibinski, L., Miller, K., Hamilton, A., & Whiteoak, C. (2018). Towards a Sequential One-Pot Preparation of 1,2,3-Benzotriazin-4(3H)-ones Employing a Key Cp*Co(III)-catalyzed C-H Amidation Step. Advanced Synthesis & Catalysis, 360 (12), 2324-2332. http://doi.org/10.1002/adsc.201800133
Liu, G., Yang, F., Li, F., Li, Z., Lang, Y., Shen, B., ... Cao, Z. (2018). Therapeutic potential of a scorpion venom-derived antimicrobial peptide and its homologs against antibiotic-resistant gram-positive bacteria. Frontiers in Microbiology, 9, 1159. http://doi.org/10.3389/fmicb.2018.01159
Harrison, P.L., Abdel-Rahman, M.A., Strong, P., Tawfik, M.M., & Miller, K. (2016). Characterisation of three alpha-helical antimicrobial peptides from the venom of Scorpio maurus palmatus. Toxicon, 117, 30-36. http://doi.org/10.1016/j.toxicon.2016.03.014
Harrison, P.L., Heath, G.R., Johnson, B.R.G., Abdel-Rahman, M.A., Strong, P., Evans, S.D., & Miller, K. (2016). Phospholipid dependent mechanism of smp24, an α-helical antimicrobial peptide from scorpion venom. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1858 (11), 2737-2744. http://doi.org/10.1016/j.bbamem.2016.07.018
Harrison, P.L., Abdel-Rahman, M., Miller, K., & Strong, P. (2014). Antimicrobial peptides from scorpion venoms. Toxicon, 88, 115-137. http://doi.org/10.1016/j.toxicon.2014.06.006
Khan, A., Miller, K., Rainsford, K., & Zhou, Y. (2013). Synthesis and Antimicrobial Activity of Novel Substituted Ethyl 2-(Quinolin-4-yl)-propanoates. Molecules, 18 (3), 3227-3240. http://doi.org/10.3390/molecules18033227
Miller, K., Dunsmore, C.J., Leeds, J.A., Patching, S.G., Sachdeva, M., Blake, K.L., ... Chopra, I. (2010). Benzothioxalone derivatives as novel inhibitors of UDP-N-acetylglucosamine enolpyruvyl transferases (MurA and MurZ). Journal of Antimicrobial Chemotherapy, 65 (12), 2566-2573. http://doi.org/10.1093/jac/dkq349
Mariner, K.R., Trowbridge, R., Agarwal, A.K., Miller, K., O'Neill, A.J., Fishwick, C.W., & Chopra, I. (2010). Furanyl-rhodanines are unattractive drug candidates for development as inhibitors of bacterial RNA polymerase. Antimicrobial Agents and Chemotherapy, 54 (10), 4506-4509. http://doi.org/10.1128/AAC.00753-10
Ooi, N., Miller, K., Randall, C., Rhys-Williams, W., Love, W., & Chopra, I. (2010). XF-70 and XF-73, novel antibacterial agents active against slow-growing and non-dividing cultures of Staphylococcus aureus including biofilms. Journal of Antimicrobial Chemotherapy, 65 (1), 72-78. http://doi.org/10.1093/jac/dkp409
Ooi, N., Miller, K., Hobbs, J., Rhys-Williams, W., Love, W., & Chopra, I. (2009). XF-73, a novel antistaphylococcal membrane-active agent with rapid bactericidal activity. Journal of Antimicrobial Chemotherapy, 64 (4), 735-740. http://doi.org/10.1093/jac/dkp299
Hobbs, J.K., Miller, K., O'Neill, A.J., & Chopra, I. (2008). Consequences of daptomycin-mediated membrane damage in Staphylococcus aureus. Journal of Antimicrobial Chemotherapy, 62 (5), 1003-1008. http://doi.org/10.1093/jac/dkn321
Dunsmore, C.J., Miller, K., Blake, K.L., Patching, S.G., Henderson, P.J.F., Garnett, J.A., ... Angeles, J.D.L. (2008). 2-Aminotetralones: Novel inhibitors of MurA and MurZ. Bioorganic & Medicinal Chemistry Letters, 18 (5), 1730-1734. http://doi.org/10.1016/j.bmcl.2008.01.089
Miller, K., O'Neill, A.J., Wilcox, M.H., Ingham, E., & Chopra, I. (2008). Delayed Development of Linezolid Resistance in Staphylococcus aureus following Exposure to Low Levels of Antimicrobial Agents. Antimicrobial Agents and Chemotherapy, 52 (6), 1940-1944. http://doi.org/10.1128/AAC.01302-07
Chopra, I., Schofield, C., Everett, M., ONeill, A., Miller, K., Wilcox, M., ... Courvalin, P. (2008). Treatment of health-care-associated infections caused by Gram-negative bacteria: a consensus statement. The Lancet Infectious Diseases, 8 (2), 133-139. http://doi.org/10.1016/S1473-3099(08)70018-5
Driffield, K., Miller, K., Bostock, J.M., O'Neill, A.J., & Chopra, I. (2008). Increased mutability of Pseudomonas aeruginosa in biofilms. Journal of Antimicrobial Chemotherapy, 61 (5), 1053-1056. http://doi.org/10.1093/jac/dkn044
Miller, K., Dunsmore, C.J., Fishwick, C.W.G., & Chopra, I. (2008). Linezolid and Tiamulin Cross-Resistance in Staphylococcus aureus Mediated by Point Mutations in the Peptidyl Transferase Center. Antimicrobial Agents and Chemotherapy, 52 (5), 1737-1742. http://doi.org/10.1128/AAC.01015-07
Driffield, K.L., Bostock, J.M., Miller, K., O'neill, A.J., Hobbs, J.K., & Chopra, I. (2006). Evolution of extended-spectrum β-lactamases in a MutS-deficient Pseudomonas aeruginosa hypermutator. The Journal of antimicrobial chemotherapy, 58 (4), 905-907. http://doi.org/10.1093/jac/dkl324
Miller, K., Storey, C., Stubbings, W.J., Hoyle, A.M., Hobbs, J.K., & Chopra, I. (2005). Antistaphylococcal activity of the novel cephalosporin CB-181963 (CAB-175). The Journal of antimicrobial chemotherapy, 55 (4), 579-582. http://doi.org/10.1093/jac/dki003
O'Neill, A.J., Miller, K., Oliva, B., & Chopra, I. (2004). Comparison of assays for detection of agents causing membrane damage in Staphylococcus aureus. The Journal of antimicrobial chemotherapy, 54 (6), 1127-1129. http://doi.org/10.1093/jac/dkh476
Oliva, B., O'Neill, A.J., Miller, K., Stubbings, W., & Chopra, I. (2004). Anti-staphylococcal activity and mode of action of clofazimine. The Journal of antimicrobial chemotherapy, 53 (3), 435-440. http://doi.org/10.1093/jac/dkh114
Miller, K., O'Neill, A.J., & Chopra, I. (2004). Escherichia coli mutators present an enhanced risk for emergence of antibiotic resistance during urinary tract infections. Antimicrobial agents and chemotherapy, 48 (1), 23-29. http://doi.org/10.1128/AAC.48.1.23-29.2004
Chopra, I., O'Neill, A.J., & Miller, K. (2003). The role of mutators in the emergence of antibiotic-resistant bacteria. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy, 6 (3), 137-145. http://doi.org/10.1016/S1368-7646(03)00041-4
Bostock, J.M., Miller, K., O'Neill, A.J., & Chopra, I. (2003). Zeocin resistance suppresses mutation in hypermutable Escherichia coli. Microbiology (Reading, England), 149 (Pt 4), 815-816. http://doi.org/10.1099/mic.0.c0111-0
Oliva, B., Miller, K., Caggiano, N., O'Neill, A.J., Cuny, G.D., Hoemann, M.Z., ... Chopra, I. (2003). Biological properties of novel antistaphylococcal quinoline-indole agents. Antimicrobial agents and chemotherapy, 47 (2), 458-466. http://doi.org/10.1128/aac.47.2.458-466.2003
Miller, K., O'Neill, A.J., & Chopra, I. (2002). Response of Escherichia coli hypermutators to selection pressure with antimicrobial agents from different classes. The Journal of antimicrobial chemotherapy, 49 (6), 925-934. http://doi.org/10.1093/jac/dkf044
Theses / Dissertations
Slater, J.E. (2024). Design and Synthesis of Potential Novel Antibiotic Compounds Utilising Photoredox Catalysis. (Doctoral thesis). Supervised by Allwood, D., Hamilton, A., & Miller, K. http://doi.org/10.7190/shu-thesis-00583
Chirila, P.G. (2021). Synthesis of valuable compounds through a cobalt-catalysed C-H functionalisation approach. (Doctoral thesis). Supervised by Whiteoak, C., Hamilton, A., & Miller, K. http://doi.org/10.7190/shu-thesis-00396
Freeman-Parry, L.E. (2020). Antimicrobial properties of wound dressings. (Doctoral thesis). Supervised by Miller, K., & Strong, P. http://doi.org/10.7190/shu-thesis-00417
Elzayat, M.T. (2017). Characterisation of novel antimicrobial peptides from Egyptian scorpion and snake venoms. (Doctoral thesis). Supervised by Miller, K., & Strong, P.
Codjoe, F.S. (2016). Detection and characterisation of carbapenem-resistant gram-negative bacilli infections in Ghana. (Doctoral thesis). Supervised by Miller, K., & Smith, T.
Harrison, P.L. (2014). The identification and characterisation of antimicrobial peptides from snake and scorpion venom. (Doctoral thesis). Supervised by Miller, K., & Strong, P.
Postgraduate supervision
01/10/2010 - 30/06/2018: Louise Freeman-Parry - Antimicrobial properties of wound dressings
05/10/2015 - 04/10/2019: Kirstie Rawson - Antimicrobial peptides from venom: structure, function & toxicity
Previous supervision:
2017: Biocidal properties of wound dressings
2017: Detection and molecular characterisation of carbapenem-resistant Gram-negative bacilli infections in selected hospitals in Ghana
2017: Characterisation of novel antimicrobial peptides and other molecules from Egyptian scorpion and snake venoms
2016: Investigating marine derived natural product scaffold: semi-synthetic and biological studies
2014: Identification and characterisation of antimicrobials from snake and scorpion venoms and haemolymph